JP2024144914A - A method for producing a radically polymerizable cross-linkable water-soluble polymer by a free radical polymerization method, which is a polymer having a polycarboxylic acid skeleton and radically polymerizable groups in block form on the side chains, in which the block copolymer connection sites migrate in a gradient manner. - Google Patents

Abstract

To provide curable compositions for medical/dental applications featured by high plasticity, little or no elution of low molecular monomers, and excellent operability.SOLUTION: Production of a polymerizable cross-linkable water-soluble polymer by using free radical polymerization can significantly reduce the production cost of the polymer, where the polymer comprises a basic skeleton of polycarboxylic acid having at least one or more radically polymerizable groups as its side chains in a block-like manner and the block copolymers gradually change at the block interface. Preparation of curable medical/dental compositions comprising such a polymer can solve the problems.SELECTED DRAWING: None

Description

The present invention relates to a method for producing a radical polymerization crosslinkable water-soluble polymer used in a novel medical/dental curable composition in the medical/dental field, which has a polycarboxylic acid as a basic skeleton and radical polymerizable groups on the side chains in blocks, and in which the block copolymer connection sites move in a gradient manner. More specifically, the present invention relates to a method for producing a radical polymerization crosslinkable water-soluble polymer used in a novel medical/dental curable composition in the medical/dental field, which has a polycarboxylic acid as a basic skeleton and radical polymerizable groups on the side chains in blocks, and in which the block copolymer connection sites move in a gradient manner.

In the fields of medicine and dentistry, zinc phosphate cements, carboxylate cements, glass ionomer cements, and resin cements have traditionally been used as filling materials for bone defects and for bonding dental prostheses, etc. Among these, resin-based restorative materials such as resin cements generally have higher toughness than zinc phosphate cements and carboxylate cements, and therefore have been widely used in the fields of orthopedics and dentistry.

However, these resin-based bioadhesive filling materials, such as resin cements, contain low-molecular-weight ethylenically unsaturated monomers such as 2-HEMA, and it has been reported that the unreacted low-molecular-weight monomers that remain even after hardening dissolve and have a significant effect on biological tissues. Furthermore, the previously mentioned carboxylate cements and glass ionomer cements have traditionally been used as materials that do not contain such low-molecular-weight ethylenically unsaturated monomers, but the hardened bodies of these materials are quite brittle, so their use is limited to certain areas.

In order to avoid these problems, the development of photopolymerizable glass ionomer cements that contain water-soluble low-molecular-weight ethylenically unsaturated group-containing monomers and polymerization initiators has been reported. However, as mentioned above, it has been reported that the unreacted low-molecular-weight monomers that remain even after hardening leach out, causing significant damage to biological tissues.

Furthermore, in Japanese Patent Laid-Open Publication No. 62-149715 and the like, polymerizable unsaturated monomers and/or oligomers and/or prepolymers containing an acid group and/or a reactive derivative group thereof have been reported. However, even if a monomer containing an acid group and an ethylenically unsaturated group in one molecule is used, it is not possible to prevent the elution of unreacted low molecular weight monomers from the hardened body, and even if a prepolymer containing an acid group and an ethylenically unsaturated group in one molecule is used, it is essential to add a large amount of a low molecular weight monomer such as 2-HEMA or Bis-GMA to the cement composition in terms of the reactivity of the ethylenically unsaturated group and the grafting rate for making it water-soluble.

Japanese Patent Application Laid-Open No. 4-173713 discloses a dental glass ionomer cement composition with improved workability, which is composed of a paste containing glass powder, a water-soluble polymer and water, and an aqueous solution of polycarboxylic acid. However, the hardened cement obtained from this composition does not have sufficient mechanical properties.

Furthermore, although the application of molecular weight-controlled polyacids to the dental field is described in detail in JP-A-2004-5162537, the application is no more than that of conventional glass ionomer cements and cannot be said to be a medical and dental hardenable composition having sufficient durability.

As described above, it has been difficult with conventional techniques to obtain a cement composition which has high toughness, is free from elution of low molecular weight monomers, and is easy to handle.

Japanese Unexamined Patent Publication No. 62-149715 Japanese Unexamined Patent Publication No. 4-173713 Special table 2004-5162537

Carboxylate cements and glass ionomer cements have been used in the medical and dental field, but the hardened bodies of these materials are very brittle, so their application is limited. To avoid these problems, the development of photopolymerizable glass ionomer cements containing water-soluble low-molecular-weight radical polymerizable group-containing monomers and polymerization initiators has been reported. However, it has been reported that the remaining unreacted low-molecular-weight monomers leach out even after hardening, causing a great impact on biological tissues. Thus, it is difficult to obtain a medical and dental hardenable composition that has high toughness, does not leach low-molecular-weight monomers, and is easy to handle using conventional techniques, and solving this problem has been an important issue.

Therefore, an object and problem of the present invention is to provide a method for producing a radical polymerization cross-linkable water-soluble polymer using a free radical polymerization method, which is an inexpensive method for producing a polymer having a polycarboxylic acid as a basic skeleton and radical polymerizable groups in block form on the side chains, in which the block copolymer connection sites migrate in a gradient, and which is used in a medical and dental curable composition having high toughness, adhesion to biological hard tissues with no or minimal elution of low molecular weight monomers, and excellent operability.

Furthermore, precise polymerization methods such as reversible addition-fragmentation chain transfer polymerization (RAFT) and atom transfer radical polymerization (ATRP) require strict anaerobic treatment and removal of residual metal catalysts, which require significant costs, but the free radical polymerization of this patent also solves these problems.

In order to solve the above-mentioned problems, the inventors and others conducted intensive research and discovered that the problems could be solved by synthesizing a radically polymerizable crosslinkable water-soluble polymer, which has a polycarboxylic acid represented by the structural formulas [Chemical Formula 1] and [Chemical Formula 2] as a basic skeleton and has radically polymerizable groups in block form on the side chains, in which the block copolymer connection sites migrate in a gradient manner, by a free radical polymerization method, and preparing a medical/dental hardenable composition containing the polymer, thereby completing the present invention. More specifically, the method includes the steps of: 1) free radical polymerization of acrylic acid ester A and/or methacrylic acid ester A by the method of claim 3; 2) adding acrylic acid ester B and/or methacrylic acid ester B to the polymer synthesized in step 1 in equal portions at least three times and block polymerizing the polymer by free radical polymerization by the method of claim 3; 3) hydrolyzing the obtained polyacrylic acid ester A and/or polymethacrylic acid ester A; 4) reacting a compound having an isocyanate group and a radical polymerizable group in the same molecule with the carboxyl group generated by the hydrolysis in step 3 through decarboxylation to form an amide bond; and 5) hydrolyzing polyacrylic acid ester B and/or polymethacrylic acid ester B to form a polycarboxylic acid. The above five steps are used to produce a radical polymerization crosslinkable water-soluble polymer having a polycarboxylic acid as a basic skeleton and radical polymerizable groups in the side chains in a block-like manner, and in which the block copolymer connection sites are gradually shifted. The inventors have found that a method for producing a radically polymerizable water-soluble polymer having a polycarboxylic acid as a basic skeleton and radically polymerizable groups in side chains in blocks, in which the block copolymer connection sites are shifted in a gradient manner, can be produced stably, easily, and at low cost through the above four steps: 1) step 1 of free radically polymerizing acrylic acid ester A and/or methacrylic acid ester A by the method described in claim 3; 2) step 2 of adding a radically polymerizable monomer having a hydroxyl group to the polymer synthesized in step 1 in equal portions at least three times and block polymerizing the polymer by free radical polymerization by the method described in claim 3; 3) step 3 of reacting a compound having an isocyanate group and a radically polymerizable group in the same molecule with the hydroxyl group of the block copolymer produced in step 2 by a urethane bond; and 4) step 4 of hydrolyzing the ester bond of polyacrylic acid ester A and/or polymethacrylic acid ester A to produce a carboxyl group, and thus the present invention has been completed. The most important and essential point of the present invention is the ester moiety structure consisting of a carboxyl group and an alcohol group of the acrylic acid ester or methacrylic acid ester used. That is, by using two kinds of acrylic acid esters or methacrylic acid esters having different electron donating properties, an ester that is easily hydrolyzed by an acid such as hydrochloric acid or trifluoroacetic acid, and an ester that is easily hydrolyzed by a base such as sodium hydroxide or potassium hydroxide are used in the synthesis of the block polymer precursor of the present invention. For example, tertiary butyl acrylate obtained by esterification of acrylic acid and tertiary butyl alcohol is easily hydrolyzed by an acid, but is resistant to bases and is difficult to hydrolyze. On the other hand, methyl acrylate obtained by esterification of acrylic acid and methyl alcohol is easily hydrolyzed by bases, is resistant to acids, and is difficult to hydrolyze. By utilizing this difference in hydrolysis, it is possible to selectively hydrolyze one of the ester moieties of the copolymer of the above-mentioned two types of monomers. Hereinafter, a specific description of the polymer produced by the production method of the present invention will be given.

In the formula, A has a chemical structure that exhibits ion reactivity, B has a chemical structure that exhibits radical polymerizability, and Grad in the formula indicates the portion that transitions from A to B in a gradient manner. Additionally, a and b indicate structures derived from a polymerization initiator or a terminator portion. In the formula, m and n indicate the number of repetitions, both of which are within the range of 1 to 1000, and A and B are covalently bonded in a gradient block shape, with a molar mass distribution Mw/Mn exceeding 1.8.

In the formula, A has a chemical structure exhibiting ion reactivity, B has a chemical structure exhibiting radical polymerizability, and Grad in the formula indicates the site where B transitions to A in a gradient manner. Additionally, a and b indicate structures derived from a polymerization initiator or a terminator portion. In the formula, m and n indicate the number of repetitions, both of which are within the range of 1 to 1000, and A and B are covalently bonded in a gradient block shape, with a molar mass distribution Mw/Mn exceeding 1.8.

The medical/dental curable composition containing the radical polymerization crosslinkable water-soluble polymer produced by the present invention, which has a polycarboxylic acid as a basic skeleton and radical polymerizable groups on the side chains in blocks, and in which the block copolymer connection sites migrate in a gradient, has higher toughness than conventional zinc phosphate cements, carboxylate cements, glass ionomer cements, and resin cements, and has the effect of obtaining a curable composition that does not elute low-molecular monomers and is easy to handle.Furthermore, the production method according to the present invention makes it possible to stably, easily, and at low cost produce the targeted radical polymerization crosslinkable water-soluble polymer, which has a polycarboxylic acid as a basic skeleton and radical polymerizable groups on the side chains in blocks, and in which the block copolymer connection sites migrate in a gradient.

A representative molecular structure of the radical polymerization crosslinkable water-soluble polymer produced in the present invention, which has a polycarboxylic acid as a basic skeleton and radical polymerizable groups in block form on the side chains, and in which the block copolymer connection sites move in a gradient manner, is shown below, and one or more of these may be used in combination.

As a chemical polymerization initiator (polymerization initiator) contained in the medical/dental curable composition containing the radical polymerization crosslinkable water-soluble polymer having the polycarboxylic acid as a basic skeleton produced by the present invention and having radical polymerizable groups in the side chains in blocks, in which the block copolymer connection site shifts in a gradient manner, an organic peroxide is preferably used. The organic peroxide used as the above-mentioned chemical polymerization initiator is not particularly limited, and any known organic peroxide can be used. Representative organic peroxides include ketone peroxides, hydroperoxides, diacyl peroxides, dialkyl peroxides, peroxyketals, peroxyesters, peroxydicarbonates, etc.

Specific examples of the ketone peroxide used as the chemical polymerization initiator include methyl ethyl ketone peroxide, methyl isobutyl ketone peroxide, methylcyclohexanone peroxide, and cyclohexanone peroxide.

Specific examples of hydroperoxides used as chemical polymerization initiators include 2,5-dimethylhexane-2,5-dihydroperoxide, diisopropylbenzene hydroperoxide, cumene hydroperoxide, tert-butyl hydroperoxide, and 1,1,3,3-tetramethylbutyl hydroperoxide.

Specific examples of diacyl peroxides used as chemical polymerization initiators include acetyl peroxide, isobutyryl peroxide, benzoyl peroxide, decanoyl peroxide, 3,5,5-trimethylhexanoyl peroxide, 2,4-dichlorobenzoyl peroxide, and lauroyl peroxide.

Specific examples of dialkyl peroxides used as chemical polymerization initiators include di-t-butyl peroxide, dicumyl peroxide, t-butylcumyl peroxide, 2,5-dimethyl-2,5-di(t-butylperoxy)hexane, 1,3-bis(t-butylperoxyisopropyl)benzene, and 2,5-dimethyl-2,5-di(t-butylperoxy)-3-hexyne.

Specific examples of peroxyketals used as chemical polymerization initiators include 1,1-bis(t-butylperoxy)-3,3,5-trimethylcyclohexane, 1,1-bis(t-butylperoxy)cyclohexane, 2,2-bis(t-butylperoxy)butane, 2,2-bis(t-butylperoxy)octane, and 4,4-bis(t-butylperoxy)valeric acid-n-butyl ester.

Specific examples of peroxy esters used as chemical polymerization initiators include α-cumyl peroxy neodecanoate, t-butyl peroxy neodecanoate, t-butyl peroxy pivalate, 2,2,4-trimethylpentyl peroxy-2-ethylhexanoate, t-amyl peroxy-2-ethylhexanoate, t-butyl peroxy-2-ethylhexanoate, di-t-butyl peroxy isophthalate, di-t-butyl peroxy hexahydroterephthalate, t-butyl peroxy-3,3,5-trimethylhexanoate, t-butyl peroxy acetate, t-butyl peroxy benzoate, and t-butyl peroxy maleric acid.

Specific examples of peroxydicarbonates used as chemical polymerization initiators include di-3-methoxyperoxydicarbonate, di-2-ethylhexylperoxydicarbonate, bis(4-t-butylcyclohexyl)peroxydicarbonate, diisopropylperoxydicarbonate, di-n-propylperoxydicarbonate, di-2-ethoxyethylperoxydicarbonate, and diallylperoxydicarbonate.

When the chemical polymerization initiator is an aqueous redox polymerization initiator system, examples of a system that can be suitably used include ammonium persulfate/ascorbic acid, potassium persulfate/ascorbic acid, and the like.

Among the organic peroxides, diacyl peroxides are preferably used from the viewpoint of the overall balance of safety, storage stability, and radical generating ability, and among them, benzoyl peroxide is particularly preferably used.

Specific examples of the polymerization accelerator include amines, sulfinic acid and its salts, borate compounds, barbituric acid derivatives, triazine compounds, copper compounds, tin compounds, vanadium compounds, halogen compounds, aldehydes, and thiol compounds.

The amines used as polymerization accelerators are divided into aliphatic amines and aromatic amines.Specific examples of aliphatic amines include n-butylamine, n-hexylamine, n-octylamine, diisopropylamine, dibutylamine, N-methyldiethanolamine, N-methylethanolamine, N-ethyldiethanolamine, Nn-butyldiethanolamine, N-lauryldiethanolamine, 2-(dimethylamino)ethyl methacrylate, N-methyldiethanolamine dimethacrylate, N-ethyldiethanolamine dimethacrylate, triethanolamine monomethacrylate, triethanolamine dimethacrylate, triethanolamine trimethacrylate, triethanolamine, trimethylamine, triethylamine, tributylamine, etc.Among these, from the viewpoint of the curability and storage stability of the composition, tertiary aliphatic amines are preferred, and N-methyldiethanolamine and triethanolamine are more preferably used.

Specific examples of aromatic amines include N,N-bis(2-hydroxyethyl)-3,5-dimethylaniline, N,N-di(2-hydroxyethyl)-p-toluidine, N,N-bis(2-hydroxyethyl)-3,4-dimethylaniline, N,N-bis(2-hydroxyethyl)-4-ethylaniline, N,N-bis(2-hydroxyethyl)-4-isopropylaniline, N,N-bis(2-hydroxyethyl)-4-t-butylaniline, N,N-bis(2-hydroxyethyl)-3,5-di-isopropylaniline, N,N-bis(2-hydroxyethyl)-3,5-di-t-butylaniline, N,N-dimethylaniline, N,N-dimethyl-p-toluidine, and N,N-dimethyl-m-toluidine. dimethylaniline, N,N-diethyl-p-toluidine, N,N-dimethyl-3,5-dimethylaniline, N,N-dimethyl-3,4-dimethylaniline, N,N-dimethyl-4-ethylaniline, N,N-dimethyl-4-isopropylaniline, N,N-dimethyl-4-t-butylaniline, N,N-dimethyl-3,5-di-t-butylaniline, 4-N,N-dimethylaminobenzoic acid ethyl ester, 4-N,N-dimethylaminobenzoic acid methyl ester, N,N-dimethylaminobenzoic acid-n-butoxyethyl ester, 4-N,N-dimethylaminobenzoic acid-2-(methacryloyloxy)ethyl ester, 4-N,N-dimethylaminobenzophenone, and 4-dimethylaminobenzoic acid butyl. Among these, from the viewpoint of imparting excellent curing properties to the composition, N,N-di(2-hydroxyethyl)-p-toluidine, 4-N,N-dimethylaminobenzoic acid ethyl ester, N,N-dimethylaminobenzoic acid-n-butoxyethyl ester, and 4-N,N-dimethylaminobenzophenone can be mentioned.

Specific examples of sulfinic acids and salts thereof used as the polymerization accelerator include p-toluenesulfinic acid, sodium p-toluenesulfinate, potassium p-toluenesulfinate, lithium p-toluenesulfinate, calcium p-toluenesulfinate, benzenesulfinic acid, sodium benzenesulfinate, potassium benzenesulfinate, lithium benzenesulfinate, calcium benzenesulfinate, 2,4,6-trimethylbenzenesulfinic acid, sodium 2,4,6-trimethylbenzenesulfinate, potassium 2,4,6-trimethylbenzenesulfinate, lithium 2,4,6-trimethylbenzenesulfinate, calcium 2,4,6-trimethylbenzenesulfinate, 2,4,6-triethylbenzenesulfinate, and the like. Examples of the sulfinic acid include benzenesulfinic acid, sodium 2,4,6-triethylbenzenesulfinate, potassium 2,4,6-triethylbenzenesulfinate, lithium 2,4,6-triethylbenzenesulfinate, calcium 2,4,6-triethylbenzenesulfinate, 2,4,6-triisopropylbenzenesulfinic acid, sodium 2,4,6-triisopropylbenzenesulfinate, potassium 2,4,6-triisopropylbenzenesulfinate, lithium 2,4,6-triisopropylbenzenesulfinate, and calcium 2,4,6-triisopropylbenzenesulfinate. Of these, sodium benzenesulfinate, sodium p-toluenesulfinate, and sodium 2,4,6-triisopropylbenzenesulfinate are particularly preferred.

Specific examples of the borate compound used as the polymerization accelerator include borate compounds having one aryl group in one molecule, such as trialkylphenyl boron, trialkyl(p-chlorophenyl) boron, trialkyl(p-fluorophenyl) boron, trialkyl(3,5-bistrifluoromethyl) phenyl boron, trialkyl[3,5-bis(1,1,1,3,3,3-hexafluoro-2-methoxy-2-propyl) phenyl] boron, trialkyl(p-nitrophenyl) boron, trialkyl(m-nitrophenyl) boron, trialkyl(p-butylphenyl) boron, trialkyl(m-butylphenyl) boron, trialkyl(p ... Examples of suitable alkyl groups include sodium salts, lithium salts, potassium salts, magnesium salts, tetrabutylammonium salts, tetramethylammonium salts, tetraethylammonium salts, methylpyridinium salts, ethylpyridinium salts, butylpyridinium salts, methylquinolinium salts, ethylquinolinium salts, and butylquinolinium salts of trialkyl(p-butyloxyphenyl)boron, trialkyl(m-butyloxyphenyl)boron, trialkyl(p-octyloxyphenyl)boron, and trialkyl(m-octyloxyphenyl)boron (wherein the alkyl group is at least one selected from the group consisting of an n-butyl group, an n-octyl group, an n-dodecyl group, and the like).

Specific examples of borate compounds having two aryl groups in one molecule include dialkyldiphenylboron, dialkyldi(p-chlorophenyl)boron, dialkyldi(p-fluorophenyl)boron, dialkyldi(3,5-bistrifluoromethyl)phenylboron, dialkyldi[3,5-bis(1,1,1,3,3,3-hexafluoro-2-methoxy-2-propyl)phenyl]boron, dialkyldi(p-nitrophenyl)boron, dialkyldi(m-nitrophenyl)boron, dialkyldi(p-butylphenyl)boron, dialkyldi(m-butylphenyl)boron, and dialkyldi(p-butyloxophenyl)boron. Examples of such salts include sodium salts, lithium salts, potassium salts, magnesium salts, tetrabutylammonium salts, tetramethylammonium salts, tetraethylammonium salts, methylpyridinium salts, ethylpyridinium salts, butylpyridinium salts, methylquinolinium salts, ethylquinolinium salts, and butylquinolinium salts of dialkyldi(m-butyloxyphenyl)boron, dialkyldi(p-octyloxyphenyl)boron, and dialkyldi(m-octyloxyphenyl)boron (wherein the alkyl group is at least one selected from the group consisting of an n-butyl group, an n-octyl group, an n-dodecyl group, and the like).

Further, specific examples of borate compounds having three aryl groups in one molecule include monoalkyltriphenylboron, monoalkyltri(p-chlorophenyl)boron, monoalkyltri(p-fluorophenyl)boron, monoalkyltri(3,5-bistrifluoromethyl)phenylboron, monoalkyltri[3,5-bis(1,1,1,3,3,3-hexafluoro-2-methoxy-2-propyl)phenyl]boron, monoalkyltri(p-nitrophenyl)boron, monoalkyltri(m-nitrophenyl)boron, monoalkyltri(p-butylphenyl)boron, monoalkyltri(m-butylphenyl)boron, monoalkyltri(p ... Examples of such an alkyl group include sodium salts, lithium salts, potassium salts, magnesium salts, tetrabutylammonium salts, tetramethylammonium salts, tetraethylammonium salts, methylpyridinium salts, ethylpyridinium salts, butylpyridinium salts, methylquinolinium salts, ethylquinolinium salts, and butylquinolinium salts of alkyltri(p-butyloxyphenyl)boron, monoalkyltri(m-butyloxyphenyl)boron, monoalkyltri(p-octyloxyphenyl)boron, and monoalkyltri(m-octyloxyphenyl)boron (wherein the alkyl group is one selected from an n-butyl group, an n-octyl group, an n-dodecyl group, and the like).

Further specific examples of borate compounds having four aryl groups in one molecule include tetraphenyl boron, tetrakis(p-chlorophenyl) boron, tetrakis(p-fluorophenyl) boron, tetrakis(3,5-bistrifluoromethyl)phenyl boron, tetrakis[3,5-bis(1,1,1,3,3,3-hexafluoro-2-methoxy-2-propyl)phenyl] boron, tetrakis(p-nitrophenyl) boron, tetrakis(m-nitrophenyl) boron, tetrakis(p-butylphenyl) boron, tetrakis(m-butylphenyl) boron, tetrakis(p-butyloxyphenyl) boron, tetrakis(m-butyloxyphenyl) boron, tetrakis(p-octyloxyphenyl) boron, Examples of the salt include sodium salts, lithium salts, potassium salts, magnesium salts, tetrabutylammonium salts, tetramethylammonium salts, tetraethylammonium salts, methylpyridinium salts, ethylpyridinium salts, butylpyridinium salts, methylquinolinium salts, ethylquinolinium salts, and butylquinolinium salts of (m-octyloxyphenyl)triphenylboron, (p-fluorophenyl)triphenylboron, (3,5-bistrifluoromethyl)phenyltriphenylboron, (p-nitrophenyl)triphenylboron, (m-butyloxyphenyl)triphenylboron, (p-butyloxyphenyl)triphenylboron, (m-octyloxyphenyl)triphenylboron, and (p-octyloxyphenyl)triphenylboron.

Among these aryl borate compounds, it is more preferable to use a borate compound having three or four aryl groups in one molecule from the viewpoint of storage stability. In addition, these aryl borate compounds can be used alone or in combination of two or more kinds.

Specific examples of barbituric acid derivatives used as polymerization accelerators include barbituric acid, 1,3-dimethylbarbituric acid, 1,3-diphenylbarbituric acid, 1,5-dimethylbarbituric acid, 5-butylbarbituric acid, 5-ethylbarbituric acid, 5-isopropylbarbituric acid, 5-cyclohexylbarbituric acid, 1,3,5-trimethylbarbituric acid, 1,3-dimethyl-5-ethylbarbituric acid, 1,3-dimethyl-n-butylbarbituric acid, 1,3-dimethyl-5-isobutylbarbituric acid, 1,3-dimethylbarbituric acid, 1,3-dimethyl-5-cyclopentylbarbituric acid, 1,3-dimethyl-5-cyclohexylbarbituric acid, 1,3-dimethyl-5-phenylbarbituric acid, 1-cyclohexyl-1-ethylbarbituric acid, 1-benzyl-5-phenylbarbituric acid, 5-methylbarbituric acid, Examples of barbituric acids include 1-cyclohexyl-5-methylbarbituric acid, 1-ethyl-5-isobutylbarbituric acid, 1,3-diethyl-5-butylbarbituric acid, 1-cyclohexyl-5-methylbarbituric acid, 1-cyclohexyl-5-ethylbarbituric acid, 1-cyclohexyl-5-octylbarbituric acid, 1-cyclohexyl-5-hexylbarbituric acid, 5-butyl-1-cyclohexylbarbituric acid, 1-benzyl-5-phenylbarbituric acid, and thiobarbituric acids, as well as salts thereof (particularly preferred are those of alkali metals or alkaline earth metals). Examples of the salts of barbituric acids include sodium 5-butylbarbiturate, sodium 1,3,5-trimethylbarbiturate, and sodium 1-cyclohexyl-5-ethylbarbiturate.

Specific examples of particularly suitable barbituric acid derivatives include 5-butylbarbituric acid, 1,3,5-trimethylbarbituric acid, 1-cyclohexyl-5-ethylbarbituric acid, 1-benzyl-5-phenylbarbituric acid, and sodium salts of these barbituric acids.

Specific examples of triazine compounds used as the polymerization accelerator include 2,4,6-tris(trichloromethyl)-s-triazine, 2,4,6-tris(tribromomethyl)-s-triazine, 2-methyl-4,6-bis(trichloromethyl)-s-triazine, 2-methyl-4,6-bis(tribromomethyl)-s-triazine, 2-phenyl-4,6-bis(trichloromethyl)-s-triazine, 2-(p-methoxyphenyl)-4,6-bis(trichloromethyl)-s-triazine, 2-(p-methylthiophenyl)-4,6-bis(trichloromethyl)-s-triazine, 2-(p-methylthiophenyl)-4,6-bis(trichloromethyl)-s-triazine, -chlorophenyl)-4,6-bis(trichloromethyl)-s-triazine, 2-(2,4-dichlorophenyl)-4,6-bis(trichloromethyl)-s-triazine, 2-(p-bromophenyl)-4,6-bis(trichloromethyl)-s-triazine, 2-(p-tolyl)-4,6-bis(trichloromethyl)-s-triazine, 2-n-propyl-4,6-bis(trichloromethyl)-s-triazine, 2-(α,α,β-trichloroethyl)-4,6-bis(trichloromethyl)-s-triazine, 2-styryl-4,6-bis(trichloromethyl)-s-triazine, 2-[2-(p-meth 2-[2-(o-methoxyphenyl)ethenyl]-4,6-bis(trichloromethyl)-s-triazine, 2-[2-(p-butoxyphenyl)ethenyl]-4,6-bis(trichloromethyl)-s-triazine, 2-[2-(3,4-dimethoxyphenyl)ethenyl]-4,6-bis(trichloromethyl)-s-triazine, 2-[2-(3,4,5-trimethoxyphenyl)ethenyl]-4,6-bis(trichloromethyl)-s-triazine, 2-(1-naphthyl)-4,6-bis(trichloromethyl)-s-triazine azine, 2-(4-biphenylyl)-4,6-bis(trichloromethyl)-s-triazine, 2-[2-{N,N-bis(2-hydroxyethyl)amino}ethoxy]-4,6-bis(trichloromethyl)-s-triazine, 2-[2-{N-hydroxyethyl-N-ethylamino}ethoxy]-4,6-bis(trichloromethyl)-s-triazine, 2-[2-{N-hydroxyethyl-N-methylamino}ethoxy]-4,6-bis(trichloromethyl)-s-triazine, 2-[2-{N-hydroxyethyl-N-methylamino}ethoxy]-4,6-bis(trichloromethyl)-s-triazine, 2-[2-{N,N-diallylamino}ethoxy]-4,6-bis(trichloromethyl)-s-triazine, and the like.

Among the above-listed triazine compounds, 2,4,6-tris(trichloromethyl)-s-triazine is particularly preferred in terms of polymerization activity, and 2-phenyl-4,6-bis(trichloromethyl)-s-triazine, 2-(p-chlorophenyl)-4,6-bis(trichloromethyl)-s-triazine, and 2-(4-biphenylyl)-4,6-bis(trichloromethyl)-s-triazine are particularly preferred in terms of storage stability. The above-listed triazine compounds may be used alone or in combination of two or more.

Specific examples of copper compounds used as the polymerization accelerator include copper acetylacetonate, copper (II) acetate, copper oleate, copper (II) chloride, and copper (II) bromide.

Specific examples of tin compounds used as polymerization accelerators include di-n-butyltin dimaleate, di-n-octyltin dimaleate, di-n-octyltin dilaurate, di-n-butyltin dilaurate, etc. Particularly suitable tin compounds are di-n-octyltin dilaurate and di-n-butyltin dilaurate.

The vanadium compound used as the polymerization accelerator is preferably a tetravalent and/or pentavalent vanadium compound. Specific examples of the tetravalent and/or pentavalent vanadium compound include divanadium(IV) tetroxide, vanadium oxide acetylacetonate(IV), vanadyl oxalate(IV), vanadyl sulfate(IV), oxo-bis(1-phenyl-1,3-butanedionato)vanadium(IV), bis(maltolato)oxo-vanadium(IV), vanadium pentoxide(V), sodium metavanadate(V), and ammonium metavanadate(V).

Specific examples of halogen compounds used as polymerization accelerators include dilauryl dimethyl ammonium chloride, lauryl dimethyl benzyl ammonium chloride, benzyl trimethyl ammonium chloride, tetramethyl ammonium chloride, benzyl dimethyl cetyl ammonium chloride, and dilauryl dimethyl ammonium bromide.

Specific examples of aldehydes used as polymerization accelerators include terephthalaldehyde and benzaldehyde derivatives. Examples of benzaldehyde derivatives include dimethylaminobenzaldehyde, p-methyloxybenzaldehyde, p-ethyloxybenzaldehyde, and pn-octyloxybenzaldehyde. Among these, pn-octyloxybenzaldehyde is preferably used from the viewpoint of curability.

Specific examples of the thiol compound used as the polymerization accelerator include 3-mercaptopropyltrimethoxysilane, 2-mercaptobenzoxazole, decanethiol, and thiobenzoic acid.

The inorganic filler used in the medical and dental hardenable composition of the present invention is not particularly limited in terms of its chemical composition, and examples thereof include silicon dioxide, alumina, silica-titania, silica-titania-barium oxide, silica-zirconia, silica-alumina, lanthanum glass, borosilicate glass, soda glass, barium glass, strontium glass, and glass ceramics.

As the acid-reactive inorganic powder used in the medical and dental hardenable composition of the present invention, barium fluoroaluminosilicate glass, strontium fluoroaluminosilicate glass, fluoroaluminosilicate glass, etc., which are used in dental glass ionomer cements, resin-reinforced glass ionomer cements, resin cements, etc., can be suitably used. The fluoroaluminosilicate glass referred to here has a basic skeleton of silicon oxide and aluminum oxide, and contains an alkali metal for introducing non-crosslinking oxygen. It further has alkaline earth metals including strontium and fluorine as modifying and coordinating ions. In addition, it is a composition in which a lanthanoid series element is incorporated into the skeleton to impart further X-ray opacity. This lanthanoid series element also participates in the composition as a modifying and coordinating ion depending on the composition range. These can be used alone or in a mixture of two or more kinds.

The composition ratio of the acid-reactive inorganic powder and the inorganic filler in the dental composition of the present invention is not particularly limited, but is preferably within the range of 25 to 90% by weight. If it is 25% by weight or less, the mechanical (physical) strength of the cured product is low, which is not preferable. Furthermore, if it is 90% by weight or more, the viscosity of the paste to be mixed is too high, which is not preferable because of poor clinical operability. Furthermore, the average particle size of the inorganic filler is preferably 0.001 to 100 μm, more preferably 0.001 to 10 μm. Furthermore, the shape of the acid-reactive inorganic powder and the inorganic filler may be either spherical or irregular.

The radical polymerizable monomer used in the medical and dental hardenable composition of the present invention may be any monomer used in the dental field without any limitation. Examples of such monomers include 7,7,9-trimethyl-4,13-dioxo-3,14-dioxa-5,12-diazahexadecane-1,16-diyl dimethacrylate (UDMA) synthesized by the urethane reaction of 2,2,4-trimethylhexamethylene diisocyanate with 2-hydroxyethyl methacrylate (HEMA), radical polymerizable monomers synthesized by the urethane reaction of HEMA or HEA with 2,4-toluylene diisocyanate, hydrogenated diphenylmethane diisocyanate, naphthalene diisocyanate, or hexamethylene diisocyanate, urethane diacrylates obtained by the reaction of aliphatic and/or aromatic diisocyanates with glycerol (meth)acrylate or 3-methacrylol-2-hydroxypropyl ester, and urethane reactants of 1,3-bis(2-isocyanato, 2-propyl)benzene with a compound having a hydroxy group. More specifically, 2,7,7,9,15-pentamethyl-4,13-dioxo-3,14-dioxa-5,12-diazahexadecane-1,16-diyl diacrylate, 2,7,7,9,15-pentamethyl-4,13-18-trioxo-3,14,17-trioxa-5,12-diazaikos-19-enyl methacrylate, 2,8,10,10,15-pentamethyl-4,13,18-trioxo-3, 14,17-trioxa-5,12-diazaikos-19-enyl methacrylate, 2,7,7,9,15-pentamethyl-4,13-dioxo-3,14-dioxa-5,12-diazahexadecane-1,16-diylbis(2-methylacrylate), 2,2'-(cyclohexane-1,2-diylbis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(propane-2,1- diyl) diacrylate, 2-((2-(((1-(acryloyloxy)propan-2-yloxy)carbonylamino)methyl)cyclohexyl)methylcarbamoyloxy)propyl methacrylate, 2,2'-(cyclohexane-1,2-diylbis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(propane-2,1-diyl)bis(2-methylacrylate), 2,2' -(bicyclo[4.1.0]heptane-3,4-diylbis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(propane-2,1-diyl)diacrylate, 2-((4-(((1-(acryloyloxy)propan-2-yloxy)carbonylamino)methyl)bicyclo[4.1.0]heptane-3-yl)methylcarbamoyloxy)propyl methacrylate, 2,2'-(bicyclo[4.1.0]heptane-3,4-diylbis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(propane-2,1-diyl)diacrylate, chloro[4.1.0]heptane-3,4-diylbis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(propane-2,1-diyl)bis(2-methylacrylate), 7,7,9-trimethyl-4,13-dioxo-3,14-dioxa-5,12-diazahexadecane-1,16-diyl diacrylate, 7,7,9-trimethyl-4,13,18-trioxo-3,14,1 7-Trioxa-5,12-diazaikos-19-enyl methacrylate, 8,10,10-trimethyl-4,13,18-trioxo-3,14,17-trioxa-5,12-diazaikos-19-enyl methacrylate, 7,7,9-trimethyl-4,13-dioxo-3,14-dioxa-5,12-diazahexadecane-1,16-diylbis(2-methylacrylate), 4,13-dioxo-3,14 -Dioxa-5,12-diazahexadecane-1,16-diyl diacrylate, 4,13,18-trioxo-3,14,17-trioxa-5,12-diazaikos-19-enyl methacrylate, 4,13-dioxo-3,14-dioxa-5,12-diazahexadecane-1,16-diyl bis(2-methylacrylate), 2-(1-(2-((2-(acryloyloxy)ethoxy)carbonylamino )-4,4-dimethylcyclohexyl)ethylcarbamoyloxy)ethyl methacrylate, 2-(1-(2-((2-(acryloyloxy)ethoxy)carbonylamino)ethyl)-5,5-dimethylcyclohexylcarbamoyloxy)ethyl methacrylate, 2-(2-(((1-(methacryloyloxy)propan-2-yloxy)carbonylamino)methyl)-2,5,5-trimethylcyclohexylcarba 2-(2-(((1-(methacryloyloxy)propan-2-yloxy)carbonylamino)methyl)-2,5,5-trimethylcyclohexylcarbamoyloxy)propane-1,3-diyl diacrylate, 2-(2-(((1-(acryloyloxy)propan-2-yloxy)carbonylamino)methyl)-2,5,5-trimethylcyclohexylcarbamoyloxy)propane-1,3-diyl diacrylate, 3-(15-(2-(acryloyloxy)ethyl)-3,12,19-trioxo-2,13,18-trioxa-4,11-diazahenicos-20-enyl)pentane-1,5-diyl diacrylate, 3-(15-(2-(acryloyloxy)ethyl)-3,12,19-trioxo-2,13,18-trioxa-4,11-diazahenicos-20-enyl)pentane-1,5-diyl diacrylate, 2,2'-(cyclohexane-1,2-diylbis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(ethane-2,1-diyl)diacrylate, 2-((2-(((2-(acryloyloxy)ethoxy)carbonylamino)methyl)cyclohexyl)methyl carboxylate, 2,2'-(cyclohexane-1,2-diylbis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(ethane-2,1-diyl)bis(2-methylacrylate), 2,15-bis(cyclohexyloxymethyl)-4,13-dioxo-3,14-dioxa-5,12-diazahexadecane-1,16-diyl diacrylate, 2,15 -Bis(cyclohexyloxymethyl)-4,13-dioxo-3,14-dioxa-5,12-diazahexadecane-1,16-diylbis(2-methylacrylate), 2,15-bis(cyclohexyloxymethyl)-4,13,18-trioxo-3,14,17-trioxa-5,12-diazaikos-19-enyl methacrylate, 1,18-bis(cyclohexyloxy)-5,14-dioxo- 4,15-dioxa-6,13-diazaoctadecane-2,17-diyl diacrylate, 1-(cyclohexyloxy)-17-(cyclohexyloxymethyl)-5,14,19-trioxo-4,15,18-trioxa-6,13-diazahenicos-20-en-2-yl methacrylate, 1,18-bis(cyclohexyloxy)-5,14-dioxo-4,15-dioxa-6,13-diazaoctadecane Can-2,17-diylbis(2-methylacrylate), 7,7,9-trimethyl-4,13-dioxo-3,14-dioxa-5,12-diazahexadecane-1,16-diylbis(2-methylacrylate), 7,7,9-trimethyl-4,13-dioxo-3,14-dioxa-5,12-diazahexadecane-1,16-diyldiacrylate, 2,2'-(1,3-phenylenebis(methylene)) Bis(azanediyl)bis(oxomethylene)bis(oxy)bis(ethane-2,1-diyl)bis(2-methacrylate), 2,2'-(1,3-phenylenebis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(ethane-2,1-diyl)diacrylate, 2-(3-(((2-(acryloyloxy)ethoxy)carbonylamino)methyl)benzylcarbamoyloxy)ethyl Methacrylate, 2,2'-(1,3-phenylenebis(methylene))bis(methylazanediyl)bis(oxomethylene)bis(oxy)bis(ethane-2,1-diyl)bis(2-methacrylate), 2,2'-(1,3-phenylenebis(methylene))bis(methylazanediyl)bis(oxomethylene)bis(oxy)bis(ethane-2,1-diyl)diacrylate, 2-((3-((((2-(acryloyloxy)ethoxy)carbonyl)(methyl)amino)methyl)benzyl)(methyl)carbamoyloxy)ethyl Methacrylate, 2,2'-(1,3-phenylenebis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(propane-2,1-diyl)bis(2-methylacrylate), 2,2'-(1,3-phenylenebis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(propane-2,1-diyl)diacrylate, 2-(3-(((2-(acryloyloxy)ethoxy)carbonylamino)methyl)benzylcarbamoyloxy)propyl methacrylate, 2-(3-(((1-(acryloyloxy)propan-2-yloxy)carbonylamino)methyl)benzylcarbamoyloxy)ethyl Methacrylate, 4,4'-(1,3-phenylenebis(methylene))bis(azanediyl)bisoxomethylene)bis(oxy)bis(4,1-phenylene)bis(2-methylacrylate), 4,4'-(1,3-phenylenebis(methylene))bis(azanediyl)bisoxomethylene)bis(oxy)bis(4,1-phenylene)diacrylate, 4-(3-(((4-(acryloxy)phenoxy)carbonylamino)methyl)benzylcarbamoyloxy)phenyl Methacrylate, 4,4'-(1,3-phenylenebis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(butane-4,1-diyl)bis(2-methylacrylate), 4,4'-(1,3-phenylenebis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(butane-4,1-diyl)diacrylate, 4-(3-(((4-(acryloyloxy)butoxy)carbonylamino)methyl)benzylcarbamoyloxy)butyl Methacrylate, 2,2'-(1,3-phenylenebis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-phenoxypropane-2,1-diyl)bis(2-methylacrylate), 2,2'-(1,3-phenylenebis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-phenoxypropane-2,1-diyl)diacrylate, 2-(3-(((1-(acryloyloxy)-3-phenoxypropan-2-yloxy)carbonylamino)methyl)benzylcarbamoyloxy)-3-phenoxypropyl Methacrylate, 2-2'-(1,3-phenylenebis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-(phenylamino)propane-2,1-diyl)bis(2-methylacrylate), 2-2'-(1,3-phenylenebis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-(phenylamino)propane-2,1-diyl)diacrylate, 2-(3-(((1-(acryloyloxy)-3-(phenylamino)propan-2-yloxy)carbonylamino)methyl)benzylcarbamoyloxy)-3-(phenylamino)propyl Methacrylate, 2,2'-(1,3 phenylenebis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-(phenylthio)propane-2,1-diyl)bis(2-methylacrylate), 2,2'-(1,3 phenylenebis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-(phenylthio)propane-2,1-diyl)diacrylate, 2-(3-(((1-(acryloxy)-3-(phenylthio)propan-2-yloxy)carbonylamino)methyl)benzylcarbamoyloxy)-3-(phenylthio)propyl Methacrylate, 2,2'-(1,3-phenylenebis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-(benzyloxy)propane-2,1-diyl)bis(2-methylacrylate), 2,2'-(1,3-phenylenebis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-(benzyloxy)propane-2,1-diyl)diacrylate, 2-(3-(((1-(acryloyloxy)-3-(benzyloxy)propan-2-yloxy)carbonylamino)methyl)benzylcarbamoyloxy)-3-(benzyloxy)propyl Methacrylate, 2,2'-(1,3-phenylenebis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-(methacryloyloxy)propane-2,1-diyl)dibenzoate, 2,2'-(1,3-phenylenebis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-(acryloyloxy)propane-2,1-diyl)dibenzoate, 2,2'-(1,3-phenylenebis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-(acryloyloxy)propane-2,1-diyl)dibenzoate 2,2'-(1,3-phenylenebis(methylene))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-(2-phenylacetoxy)propane-2,1-diyl)diacrylate, 2-(3-(((1-(acryloyloxy)-3-(2-phenylacetoxy)propan-2-yloxy)carbonylamino)methyl)benzylcarbamoyloxy)-3-(2-phenylacetoxy)propyl Methacrylate 2,2'-(2,2'-(1,3-phenylene)bis(propane-2.2-diyl))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(ethane-2,1-diyl)bis(2-methacrylate), 2,2'-(2,2'-(1,3-phenylene)bis(propane-2.2-diyl))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(ethane-2,1-diyl)diacrylate, 2-(2-(3-(2-((2-(acryloyloxy)ethoxy)carbonylamino)propan-2-yl)phenyl)propan-2-ylcarbamoyloxy)ethyl methacrylate, 2, 2'-(2,2'-(1,3-phenylene)bis(propane-2,2-diyl))bis(methylazanediyl)bis(oxomethylene)bis(oxy)bis(ethane-2,1-diyl)bis(2-methacrylate), 2,2'-(2,2'-(1,3-phenylene)bis(propane-2,2-diyl))bis(methylazanediyl)bis(oxomethylene)bis(oxy)bis(ethane-2,1-diyl)diacrylate, 2-((2-(3-(2-(((2-(acryloyloxy)ethoxy)carbonyl)(methyl)amino)propan-2-yl)phenyl)propan-2-yl)(methyl)carbamoyloxy)ethyl Methacrylate, 2,2'-(2,2'-(1,3-phenylene)bis(propane-2,2-diyl))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(propane-2,1-diyl)bis(2-methylacrylate), 2,2'-(2,2'-(1,3-phenylene)bis(propane-2,2-diyl))bis(azanediyl)bis(oxomethylene)bis(oxy)bis 2-(2-(3-(2-((2-(acryloyloxy)ethoxy)carbonylamino)propan-2-yl)phenyl)propan-2-ylcarbamoyloxy)propyl methacrylate, 2-(2-(3-(2-((1-(acryloyloxy)propan-2-yloxy)carbonylamino)propan-2-ylcarbamoyloxy)ethyl Methacrylate, 4,4'-(2,2'-(1,3-phenylene)bis(propane-2,2-diyl))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(4,1-phenylene)bis(2-methylacrylate), 4,4'-(2,2'-(1,3-phenylene)bis(propane-2,2-diyl))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(4,1-phenylene)diacrylate, 4-(2-(3-(2-((4-(acryloyloxy)phenoxy)carbonylamino)propan-2-yl)phenyl )propan-2-ylcarbamoyloxy)phenyl methacrylate, 4,4'-(2,2'-(1,3-phenylene)bis(propane-2,2-diyl))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(butane-4,1-diyl)bis(2-methacrylate), 4,4'-(2,2'-(1,3-phenylene)bis(propane-2,2-diyl))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(butane-4,1-diyl)diacrylate, 4-(2-(3-(2-((4-acryloyloxy)butoxy) carbonylamino)propan-2-yl)phenyl)propan-2-ylcarbamoyloxy)butyl methacrylate, 2,2'-(2,2'-(1,3-phenylene)bis(propane-2,2-diyl))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-phenoxypropane-2,1-diyl)bis(2-methacrylate), 2,2'-(2,2'-(1,3-phenylene)bis(propane-2,2-diyl))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-phenoxypropane-2,1-diyl)diacrylate, 2-(2-(3-(2-((1-(acryloyloxy)-3-phenoxypropan-2-yloxy) (carbonylamino)propan-2-yl)phenyl)propan-2-ylcarbamoyloxy)-3-phenoxypropyl Methacrylate, 2,2'-(2,2'-(1,3-phenylene)bis(propane-2,2-diyl))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-(phenylamino)propane-2,1-diyl)bis(2-methacrylate), 2,2'-(2,2'-(1,3-phenylene)bis(propane-2,2-diyl))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-(phenylamino)propane-2,1-diyl)diacrylate, 2-(2-(3-(2-((1-(acryloyloxy)-3-(phenylamino)propan-2-yloxy)carbonylamino)propan-2-yl)phenyl)propan-2-ylcarbamoyloxy)-3-(phenylamino)propyl Methacrylate, 2,2'-(2,2'-(1,3-phenylene)bis(propane-2,2-diyl))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-(phenylthio)propane-2,1-diyl)bis(2-methylacrylate), 2,2'-(2,2'-(1,3-phenylene)bis(propane-2,2-diyl))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-(phenylthio)propane-2,1-diyl)diacrylate, 2-(2-(3-(2-((1-(acryloyloxy)-3-(phenylthio)propan-2-yloxy)carbonylamino)propan-2-yl)phenyl)propan-2-ylcarbamoyloxy)-3-(phenylthio)propyl Methacrylate, 2-2'-(2,2'-(1,3-phenylene)bis(propane-2,2-diyl))bis(azanediyl)bis(oxomethylene)bis(3-(benzyloxy)propane-2,1-diyl)bis(2-methylacrylate), 2-2'-(2,2'-(1,3-phenylene)bis(propane-2,2-diyl))bis(azanediyl)bis(oxomethylene)bis(3-(benzyloxy)propane-2,1-diyl)diacrylate, 2-(2-(3-(2-((1-(acryloyloxy)-3-(benzyloxy)propan-2-yloxy)carbonylamino)propan-2-yl)phenyl)propan-2-ylcarbamoyloxy)-3-(benzyloxy)propyl Methacrylate, 2,2'-(2,2'-(1,3-phenylene)bis(propane-2,2-diyl))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-(methacryloyloxy)propane-2,1-diyl)dibenzoate, 2,2'-(2,2'-(1,3-phenylene)bis(propane-2,2-diyl))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-(acryloyloxy)propane-2,1-diyl)dibenzoate, 2,2'-(2,2'-(1,3-phenylene)bis(propane-2,2-diyl))bis(azanediyl)bis(oxomethylene )bis(oxy)bis(3-(2-phenylacetoxy)propane-2,1-diyl)bis(2-methacrylate), 2,2'-(2,2'-(1,3-phenylene)bis(propane-2,2-diyl))bis(azanediyl)bis(oxomethylene)bis(oxy)bis(3-(2-phenylacetoxy)propane-2,1-diyl)diacrylate, 2-(2-(3-(2-((1-(acryloyloxy)-3-(2-phenylacetoxy)propan-2-yloxy)carbonylamino)propan-2-yl)phenyl)propan-2-ylcarbamoyloxy)-3-(2-phenylacetoxy)propyl methacrylate, and the like.

The polymerization initiator contained in the medical and dental hardenable composition of the present invention can be selected from polymerization initiators used in the industrial field, and among them, polymerization initiators used for dental applications are preferably used. In particular, photopolymerization and chemical polymerization initiators are used alone or in appropriate combination of two or more. Specifically, photopolymerization initiators among the polymerization initiators contained in the medical and dental hardenable composition of the present invention include (bis)acylphosphine oxides, water-soluble acylphosphine oxides, thioxanthones or quaternary ammonium salts of thioxanthones, ketals, α-diketones, coumarins, anthraquinones, benzoin alkyl ether compounds, and α-aminoketone compounds. The ratio of these to the radical polymerizable monomer is preferably 0.5 wt% to 5 wt%. At a concentration lower than 0.5 wt%, the amount of unpolymerized radical polymerizable monomer increases, resulting in a decrease in mechanical strength. At a concentration higher than 5 wt%, the degree of polymerization decreases, resulting in a decrease in mechanical strength.

Specific examples of acylphosphine oxides used as photopolymerization initiators include 2,4,6-trimethylbenzoyldiphenylphosphine oxide, 2,6-dimethoxybenzoyldiphenylphosphine oxide, 2,6-dichlorobenzoyldiphenylphosphine oxide, 2,4,6-trimethylbenzoylmethoxyphenylphosphine oxide, 2,4,6-trimethylbenzoylethoxyphenylphosphine oxide, 2,3,5,6-tetramethylbenzoyldiphenylphosphine oxide, and benzoyldi-(2,6-dimethylphenyl)phosphonate. Examples of the bisacylphosphine oxides include bis-(2,6-dichlorobenzoyl)phenylphosphine oxide, bis-(2,6-dichlorobenzoyl)-2,5-dimethylphenylphosphine oxide, bis-(2,6-dichlorobenzoyl)-4-propylphenylphosphine oxide, bis-(2,6-dichlorobenzoyl)-1-naphthylphosphine oxide, bis-(2,6-dimethoxybenzoyl)phenylphosphine oxide, bis-(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentylphosphine oxide, bis-(2,6-dimethoxybenzoyl)-2,5-dimethylphenylphosphine oxide, bis-(2,4,6-trimethylbenzoyl)phenylphosphine oxide, and (2,5,6-trimethylbenzoyl)-2,4,4-trimethylpentylphosphine oxide.

Specific examples of thioxanthones or quaternary ammonium salts of thioxanthones used as photopolymerization initiators include thioxanthones, 2-chlorothioxanthen-9-one, 2-hydroxy-3-(9-oxy-9H-thioxanthen-4-yloxy)-N,N,N-trimethyl-propanaminium chloride, 2-hydroxy-3-(1-methyl-9-oxy-9H-thioxanthen-4-yloxy)-N,N,N-trimethyl-propanaminium chloride, 2-hydroxy-3-(9-oxo-9H-thioxanthen-2-yloxy)-N,N,N-trimethyl-propanaminium chloride, , N,N-trimethyl-propanaminium chloride, 2-hydroxy-3-(3,4-dimethyl-9-oxo-9H-thioxanthen-2-yloxy)-N,N,N-trimethyl-1-propanaminium chloride, 2-hydroxy-3-(3,4-dimethyl-9H-thioxanthen-2-yloxy)-N,N,N-trimethyl-1-propanaminium chloride, 2-hydroxy-3-(1,3,4-trimethyl-9-oxo-9H-thioxanthen-2-yloxy)-N,N,N-trimethyl-1-propanaminium chloride, and the like.

Specific examples of α-diketones used as photopolymerization initiators include diacetyl, dibenzyl, camphorquinone, 2,3-pentadione, 2,3-octadione, 9,10-phenanthrenequinone, 4,4'-oxybenzyl, and acenaphthenequinone.

Specific examples of coumarin compounds used as photopolymerization initiators include 3,3'-carbonylbis(7-diethylamino)coumarin, 3-(4-methoxybenzoyl)coumarin, 3-chenoylcoumarin, 3-benzoyl-5,7-dimethoxycoumarin, 3-benzoyl-7-methoxycoumarin, 3-benzoyl-6-methoxycoumarin, 3-benzoyl-8-methoxycoumarin, 3-benzoylcoumarin, 7-methoxy-3-(p-nitrobenzoyl)coumarin, 3-(p-nitrobenzoyl)coumarin, 3-benzoyl-8-methoxycoumarin, 3,5-carbonylbis(7-methoxycoumarin), 3-benzoyl-6-bromocoumarin, 3,3'-carbonylbiscoumarin, 3-benzoyl-7-dimethylaminocoumarin, 3-benzoyl-8-methoxycoumarin, 3,5-carbonylbis(7-methoxycoumarin), 3-benzoyl-6-bromocoumarin, 3,3'-carbonylbiscoumarin, 3-benzoyl-7-dimethylaminocoumarin, 3-benzoyl-8-methoxycoumarin, 3,5-carbonylbis(7-methoxycoumarin), 3-benzoyl-6-bromocoumarin, 3,5-carbonylbis(7-methoxycoumarin), 3-benzoyl-8-methoxy ... 3-(4-nitrobenzoyl)coumarin, 7-methoxy-3-(4-nitrobenzoyl)coumarin, 7-diethylamino-3-(4-methoxybenzoyl)coumarin, 7-diethylamino-3-(4-methoxybenzoyl)coumarin, 7-diethylamino-3-(4-diethylamino)coumarin, 7-methoxy-3-(4-methoxybenzoyl)coumarin, 7-diethylamino-3-(4-diethylamino)coumarin, 7-methoxy-3-(4-methoxybenzoyl)coumarin, 3-(4-nitrobenzoyl ... 3-(4-benzothiazoyl)benzo[f]coumarin, 3-(4-ethoxycinnamoyl)-7-methoxycoumarin, 3-(4-dimethylaminocinnamoyl)coumarin, 3-(4-diphenylaminocinnamoyl)coumarin, 3-[(3-dimethylbenzothiazol-2-ylidene)acetyl]coumarin, 3-[(1-methylnaphtho[1,2-d]thiazol-2-ylidene)acetyl]coumarin, 3,3'-carbonylbis(6-methoxycoumarin), 3,3'-carbonylbis(7-acetoxycoumarin), 3,3'-carbonylbis(7-dimethylaminocoumarin), 3-(2-benzothiazoyl)-7-(diethylamino)coumarin, 3-(2-benzothiazoyl)-7-(dibutylamino)coumarin, 3-(2-benzimidazoyl)-7-(diethylamino ) coumarin, 3-(2-benzothiazoyl)-7-(dioctylamino) coumarin, 3-acetyl-7-(dimethylamino) coumarin, 3,3'-carbonylbis(7-dibutylaminocoumarin), 3,3'-carbonyl-7-diethylaminocoumarin-7'-bis(butoxyethyl)aminocoumarin, 10-[3-[4-(dimethylamino)phenyl]-1-oxo-2-propenyl]-2,3,6,7-1,1,7,7-tetramethyl1H,5H,11H-[1]benzopyrano[6,7,8-ij]quinolizin-11-one, 10-(2-benzothiazoyl)-2,3,6,7-tetrahydro-1,1,7,7-tetramethyl1H,5H,11H-[1]benzopyrano[6,7,8-ij]quinolizin-11-one, and the like.

Among the coumarin compounds, 3,3'-carbonylbis(7-diethylaminocoumarin) and 3,3'-carbonylbis(7-dibutylaminocoumarin) are particularly preferred.

Specific examples of anthraquinones used as photopolymerization initiators include anthraquinone, 1-chloroanthraquinone, 2-chloroanthraquinone, 1-bromoanthraquinone, 1,2-benzanthraquinone, 1-methylanthraquinone, 2-ethylanthraquinone, and 1-hydroxyanthraquinone.

Specific examples of benzoin alkyl ethers used as photopolymerization initiators include benzoin methyl ether, benzoin ethyl ether, benzoin isopropyl ether, and benzoin isobutyl ether.

Specific examples of α-aminoketones used as photopolymerization initiators include 2-methyl-1-[4-(methylthio)phenyl]-2-morpholinopropan-1-one.

Among the photopolymerization initiators, it is preferable to use at least one selected from the group consisting of (bis)acylphosphine oxides and their salts, α-diketones, and coumarin compounds, which provides a composition that is excellent in photocurability in the visible and near ultraviolet regions and exhibits sufficient photocurability using any of the light sources, such as a halogen lamp, a light-emitting diode (LED), and a xenon lamp.

Among the polymerization initiators contained in the medical and dental hardenable composition of the present invention, organic peroxides are preferably used as the chemical polymerization initiator. The organic peroxides used as the above-mentioned chemical polymerization initiator are not particularly limited, and known ones can be used. Representative organic peroxides include ketone peroxides, hydroperoxides, diacyl peroxides, dialkyl peroxides, peroxyketals, peroxyesters, and peroxydicarbonates.

Specific examples of the ketone peroxide used as the chemical polymerization initiator include methyl ethyl ketone peroxide, methyl isobutyl ketone peroxide, methylcyclohexanone peroxide, and cyclohexanone peroxide.

Specific examples of hydroperoxides used as chemical polymerization initiators include 2,5-dimethylhexane-2,5-dihydroperoxide, diisopropylbenzene hydroperoxide, cumene hydroperoxide, t-butyl hydroperoxide, and 1,1,3,3-tetramethylbutyl hydroperoxide.

Specific examples of diacyl peroxides used as chemical polymerization initiators include acetyl peroxide, isobutyryl peroxide, benzoyl peroxide, decanoyl peroxide, 3,5,5-trimethylhexanoyl peroxide, 2,4-dichlorobenzoyl peroxide, and lauroyl peroxide.

Specific examples of dialkyl peroxides used as chemical polymerization initiators include di-t-butyl peroxide, dicumyl peroxide, t-butylcumyl peroxide, 2,5-dimethyl-2,5-di(t-butylperoxy)hexane, 1,3-bis(t-butylperoxyisopropyl)benzene, and 2,5-dimethyl-2,5-di(t-butylperoxy)-3-hexyne.

Specific examples of peroxyketals used as chemical polymerization initiators include 1,1-bis(t-butylperoxy)-3,3,5-trimethylcyclohexane, 1,1-bis(t-butylperoxy)cyclohexane, 2,2-bis(t-butylperoxy)butane, 2,2-bis(t-butylperoxy)octane, and 4,4-bis(t-butylperoxy)valeric acid-n-butyl ester.

Specific examples of peroxy esters used as chemical polymerization initiators include α-cumyl peroxy neodecanoate, t-butyl peroxy neodecanoate, t-butyl peroxy pivalate, 2,2,4-trimethylpentyl peroxy-2-ethylhexanoate, t-amyl peroxy-2-ethylhexanoate, t-butyl peroxy-2-ethylhexanoate, di-t-butyl peroxy isophthalate, di-t-butyl peroxy hexahydroterephthalate, t-butyl peroxy-3,3,5-trimethylhexanoate, t-butyl peroxy acetate, t-butyl peroxy benzoate, and t-butyl peroxy maleric acid.

Specific examples of peroxydicarbonates used as chemical polymerization initiators include di-3-methoxyperoxydicarbonate, di-2-ethylhexylperoxydicarbonate, bis(4-t-butylcyclohexyl)peroxydicarbonate, diisopropylperoxydicarbonate, di-n-propylperoxydicarbonate, di-2-ethoxyethylperoxydicarbonate, and diallylperoxydicarbonate.

Among the organic peroxides, diacyl peroxides are preferably used from the viewpoint of the overall balance of safety, storage stability, and radical generating ability, and among them, benzoyl peroxide is particularly preferably used.

Specific examples of the polymerization accelerator include amines, sulfinic acid and its salts, borate compounds, barbituric acid derivatives, triazine compounds, copper compounds, tin compounds, vanadium compounds, halogen compounds, aldehydes, and thiol compounds.

The amines used as polymerization accelerators are divided into aliphatic amines and aromatic amines.Specific examples of aliphatic amines include n-butylamine, n-hexylamine, n-octylamine, diisopropylamine, dibutylamine, N-methyldiethanolamine, N-methylethanolamine, N-ethyldiethanolamine, Nn-butyldiethanolamine, N-lauryldiethanolamine, 2-(dimethylamino)ethyl methacrylate, N-methyldiethanolamine dimethacrylate, N-ethyldiethanolamine dimethacrylate, triethanolamine monomethacrylate, triethanolamine dimethacrylate, triethanolamine trimethacrylate, triethanolamine, trimethylamine, triethylamine, tributylamine, etc.Among these, from the viewpoint of the curability and storage stability of the composition, tertiary aliphatic amines are preferred, and N-methyldiethanolamine and triethanolamine are more preferably used.

Specific examples of aromatic amines include N,N-bis(2-hydroxyethyl)-3,5-dimethylaniline, N,N-di(2-hydroxyethyl)-p-toluidine, N,N-bis(2-hydroxyethyl)-3,4-dimethylaniline, N,N-bis(2-hydroxyethyl)-4-ethylaniline, N,N-bis(2-hydroxyethyl)-4-isopropylaniline, N,N-bis(2-hydroxyethyl)-4-t-butylaniline, N,N-bis(2-hydroxyethyl)-3,5-di-isopropylaniline, N,N-bis(2-hydroxyethyl)-3,5-di-t-butylaniline, N,N-dimethylaniline, N,N-dimethyl-p-toluidine, and N,N-dimethyl-m-toluidine. dimethylaniline, N,N-diethyl-p-toluidine, N,N-dimethyl-3,5-dimethylaniline, N,N-dimethyl-3,4-dimethylaniline, N,N-dimethyl-4-ethylaniline, N,N-dimethyl-4-isopropylaniline, N,N-dimethyl-4-t-butylaniline, N,N-dimethyl-3,5-di-t-butylaniline, 4-N,N-dimethylaminobenzoic acid ethyl ester, 4-N,N-dimethylaminobenzoic acid methyl ester, N,N-dimethylaminobenzoic acid-n-butoxyethyl ester, 4-N,N-dimethylaminobenzoic acid-2-(methacryloyloxy)ethyl ester, 4-N,N-dimethylaminobenzophenone, and 4-dimethylaminobenzoic acid butyl. Among these, from the viewpoint of imparting excellent curing properties to the composition, N,N-di(2-hydroxyethyl)-p-toluidine, 4-N,N-dimethylaminobenzoic acid ethyl ester, N,N-dimethylaminobenzoic acid-n-butoxyethyl ester, and 4-N,N-dimethylaminobenzophenone can be mentioned.

Specific examples of sulfinic acids and salts thereof used as the polymerization accelerator include p-toluenesulfinic acid, sodium p-toluenesulfinate, potassium p-toluenesulfinate, lithium p-toluenesulfinate, calcium p-toluenesulfinate, benzenesulfinic acid, sodium benzenesulfinate, potassium benzenesulfinate, lithium benzenesulfinate, calcium benzenesulfinate, 2,4,6-trimethylbenzenesulfinic acid, sodium 2,4,6-trimethylbenzenesulfinate, potassium 2,4,6-trimethylbenzenesulfinate, lithium 2,4,6-trimethylbenzenesulfinate, calcium 2,4,6-trimethylbenzenesulfinate, 2,4,6-triethylbenzenesulfinate, and the like. Examples of the sulfinic acid include benzenesulfinic acid, sodium 2,4,6-triethylbenzenesulfinate, potassium 2,4,6-triethylbenzenesulfinate, lithium 2,4,6-triethylbenzenesulfinate, calcium 2,4,6-triethylbenzenesulfinate, 2,4,6-triisopropylbenzenesulfinic acid, sodium 2,4,6-triisopropylbenzenesulfinate, potassium 2,4,6-triisopropylbenzenesulfinate, lithium 2,4,6-triisopropylbenzenesulfinate, and calcium 2,4,6-triisopropylbenzenesulfinate. Of these, sodium benzenesulfinate, sodium p-toluenesulfinate, and sodium 2,4,6-triisopropylbenzenesulfinate are particularly preferred.

Specific examples of the borate compound used as the polymerization accelerator include borate compounds having one aryl group in one molecule, such as trialkylphenyl boron, trialkyl(p-chlorophenyl) boron, trialkyl(p-fluorophenyl) boron, trialkyl(3,5-bistrifluoromethyl) phenyl boron, trialkyl[3,5-bis(1,1,1,3,3,3-hexafluoro-2-methoxy-2-propyl) phenyl] boron, trialkyl(p-nitrophenyl) boron, trialkyl(m-nitrophenyl) boron, trialkyl(p-butylphenyl) boron, trialkyl(m-butylphenyl) boron, trialkyl(p ... Examples of suitable alkyl groups include sodium salts, lithium salts, potassium salts, magnesium salts, tetrabutylammonium salts, tetramethylammonium salts, tetraethylammonium salts, methylpyridinium salts, ethylpyridinium salts, butylpyridinium salts, methylquinolinium salts, ethylquinolinium salts, and butylquinolinium salts of trialkyl(p-butyloxyphenyl)boron, trialkyl(m-butyloxyphenyl)boron, trialkyl(p-octyloxyphenyl)boron, and trialkyl(m-octyloxyphenyl)boron (wherein the alkyl group is at least one selected from the group consisting of an n-butyl group, an n-octyl group, an n-dodecyl group, and the like).

Specific examples of borate compounds having two aryl groups in one molecule include dialkyldiphenylboron, dialkyldi(p-chlorophenyl)boron, dialkyldi(p-fluorophenyl)boron, dialkyldi(3,5-bistrifluoromethyl)phenylboron, dialkyldi[3,5-bis(1,1,1,3,3,3-hexafluoro-2-methoxy-2-propyl)phenyl]boron, dialkyldi(p-nitrophenyl)boron, dialkyldi(m-nitrophenyl)boron, dialkyldi(p-butylphenyl)boron, dialkyldi(m-butylphenyl)boron, and dialkyldi(p-butyloxophenyl)boron. Examples of such salts include sodium salts, lithium salts, potassium salts, magnesium salts, tetrabutylammonium salts, tetramethylammonium salts, tetraethylammonium salts, methylpyridinium salts, ethylpyridinium salts, butylpyridinium salts, methylquinolinium salts, ethylquinolinium salts, and butylquinolinium salts of dialkyldi(m-butyloxyphenyl)boron, dialkyldi(p-octyloxyphenyl)boron, and dialkyldi(m-octyloxyphenyl)boron (wherein the alkyl group is at least one selected from the group consisting of an n-butyl group, an n-octyl group, an n-dodecyl group, and the like).

Further, specific examples of borate compounds having three aryl groups in one molecule include monoalkyltriphenylboron, monoalkyltri(p-chlorophenyl)boron, monoalkyltri(p-fluorophenyl)boron, monoalkyltri(3,5-bistrifluoromethyl)phenylboron, monoalkyltri[3,5-bis(1,1,1,3,3,3-hexafluoro-2-methoxy-2-propyl)phenyl]boron, monoalkyltri(p-nitrophenyl)boron, monoalkyltri(m-nitrophenyl)boron, monoalkyltri(p-butylphenyl)boron, monoalkyltri(m-butylphenyl)boron, monoalkyltri(p ... Examples of such an alkyl group include sodium salts, lithium salts, potassium salts, magnesium salts, tetrabutylammonium salts, tetramethylammonium salts, tetraethylammonium salts, methylpyridinium salts, ethylpyridinium salts, butylpyridinium salts, methylquinolinium salts, ethylquinolinium salts, and butylquinolinium salts of alkyltri(p-butyloxyphenyl)boron, monoalkyltri(m-butyloxyphenyl)boron, monoalkyltri(p-octyloxyphenyl)boron, and monoalkyltri(m-octyloxyphenyl)boron (wherein the alkyl group is one selected from an n-butyl group, an n-octyl group, an n-dodecyl group, and the like).

Further specific examples of borate compounds having four aryl groups in one molecule include tetraphenyl boron, tetrakis(p-chlorophenyl) boron, tetrakis(p-fluorophenyl) boron, tetrakis(3,5-bistrifluoromethyl)phenyl boron, tetrakis[3,5-bis(1,1,1,3,3,3-hexafluoro-2-methoxy-2-propyl)phenyl] boron, tetrakis(p-nitrophenyl) boron, tetrakis(m-nitrophenyl) boron, tetrakis(p-butylphenyl) boron, tetrakis(m-butylphenyl) boron, tetrakis(p-butyloxyphenyl) boron, tetrakis(m-butyloxyphenyl) boron, tetrakis(p-octyloxyphenyl) boron, Examples of the salt include sodium salts, lithium salts, potassium salts, magnesium salts, tetrabutylammonium salts, tetramethylammonium salts, tetraethylammonium salts, methylpyridinium salts, ethylpyridinium salts, butylpyridinium salts, methylquinolinium salts, ethylquinolinium salts, and butylquinolinium salts of (m-octyloxyphenyl)triphenylboron, (p-fluorophenyl)triphenylboron, (3,5-bistrifluoromethyl)phenyltriphenylboron, (p-nitrophenyl)triphenylboron, (m-butyloxyphenyl)triphenylboron, (p-butyloxyphenyl)triphenylboron, (m-octyloxyphenyl)triphenylboron, and (p-octyloxyphenyl)triphenylboron.

Among these aryl borate compounds, it is more preferable to use a borate compound having three or four aryl groups in one molecule from the viewpoint of storage stability. In addition, these aryl borate compounds can be used alone or in combination of two or more kinds.

Specific examples of barbituric acid derivatives used as polymerization accelerators include barbituric acid, 1,3-dimethylbarbituric acid, 1,3-diphenylbarbituric acid, 1,5-dimethylbarbituric acid, 5-butylbarbituric acid, 5-ethylbarbituric acid, 5-isopropylbarbituric acid, 5-cyclohexylbarbituric acid, 1,3,5-trimethylbarbituric acid, 1,3-dimethyl-5-ethylbarbituric acid, 1,3-dimethyl-n-butylbarbituric acid, 1,3-dimethyl-5-isobutylbarbituric acid, 1,3-dimethylbarbituric acid, 1,3-dimethyl-5-cyclopentylbarbituric acid, 1,3-dimethyl-5-cyclohexylbarbituric acid, 1,3-dimethyl-5-phenylbarbituric acid, 1-cyclohexyl-1-ethylbarbituric acid, 1-benzyl-5-phenylbarbituric acid, 5-methylbarbituric acid, Examples of barbituric acids include 1-cyclohexyl-5-methylbarbituric acid, 1-ethyl-5-isobutylbarbituric acid, 1,3-diethyl-5-butylbarbituric acid, 1-cyclohexyl-5-methylbarbituric acid, 1-cyclohexyl-5-ethylbarbituric acid, 1-cyclohexyl-5-octylbarbituric acid, 1-cyclohexyl-5-hexylbarbituric acid, 5-butyl-1-cyclohexylbarbituric acid, 1-benzyl-5-phenylbarbituric acid, and thiobarbituric acids, as well as salts thereof (particularly preferred are those of alkali metals or alkaline earth metals). Examples of the salts of barbituric acids include sodium 5-butylbarbiturate, sodium 1,3,5-trimethylbarbiturate, and sodium 1-cyclohexyl-5-ethylbarbiturate.

Specific examples of particularly suitable barbituric acid derivatives include 5-butylbarbituric acid, 1,3,5-trimethylbarbituric acid, 1-cyclohexyl-5-ethylbarbituric acid, 1-benzyl-5-phenylbarbituric acid, and sodium salts of these barbituric acids.

Specific examples of triazine compounds used as the polymerization accelerator include 2,4,6-tris(trichloromethyl)-s-triazine, 2,4,6-tris(tribromomethyl)-s-triazine, 2-methyl-4,6-bis(trichloromethyl)-s-triazine, 2-methyl-4,6-bis(tribromomethyl)-s-triazine, 2-phenyl-4,6-bis(trichloromethyl)-s-triazine, 2-(p-methoxyphenyl)-4,6-bis(trichloromethyl)-s-triazine, 2-(p-methylthiophenyl)-4,6-bis(trichloromethyl)-s-triazine, 2-(p-methylthiophenyl)-4,6-bis(trichloromethyl)-s-triazine, -chlorophenyl)-4,6-bis(trichloromethyl)-s-triazine, 2-(2,4-dichlorophenyl)-4,6-bis(trichloromethyl)-s-triazine, 2-(p-bromophenyl)-4,6-bis(trichloromethyl)-s-triazine, 2-(p-tolyl)-4,6-bis(trichloromethyl)-s-triazine, 2-n-propyl-4,6-bis(trichloromethyl)-s-triazine, 2-(α,α,β-trichloroethyl)-4,6-bis(trichloromethyl)-s-triazine, 2-styryl-4,6-bis(trichloromethyl)-s-triazine, 2-[2-(p-meth 2-[2-(o-methoxyphenyl)ethenyl]-4,6-bis(trichloromethyl)-s-triazine, 2-[2-(p-butoxyphenyl)ethenyl]-4,6-bis(trichloromethyl)-s-triazine, 2-[2-(3,4-dimethoxyphenyl)ethenyl]-4,6-bis(trichloromethyl)-s-triazine, 2-[2-(3,4,5-trimethoxyphenyl)ethenyl]-4,6-bis(trichloromethyl)-s-triazine, 2-(1-naphthyl)-4,6-bis(trichloromethyl)-s-triazine azine, 2-(4-biphenylyl)-4,6-bis(trichloromethyl)-s-triazine, 2-[2-{N,N-bis(2-hydroxyethyl)amino}ethoxy]-4,6-bis(trichloromethyl)-s-triazine, 2-[2-{N-hydroxyethyl-N-ethylamino}ethoxy]-4,6-bis(trichloromethyl)-s-triazine, 2-[2-{N-hydroxyethyl-N-methylamino}ethoxy]-4,6-bis(trichloromethyl)-s-triazine, 2-[2-{N-hydroxyethyl-N-methylamino}ethoxy]-4,6-bis(trichloromethyl)-s-triazine, 2-[2-{N,N-diallylamino}ethoxy]-4,6-bis(trichloromethyl)-s-triazine, and the like.

Among the above-listed triazine compounds, 2,4,6-tris(trichloromethyl)-s-triazine is particularly preferred in terms of polymerization activity, and 2-phenyl-4,6-bis(trichloromethyl)-s-triazine, 2-(p-chlorophenyl)-4,6-bis(trichloromethyl)-s-triazine, and 2-(4-biphenylyl)-4,6-bis(trichloromethyl)-s-triazine are particularly preferred in terms of storage stability. The above-listed triazine compounds may be used alone or in combination of two or more.

Specific examples of copper compounds used as the polymerization accelerator include copper acetylacetonate, copper (II) acetate, copper oleate, copper (II) chloride, and copper (II) bromide.

Specific examples of tin compounds used as polymerization accelerators include di-n-butyltin dimaleate, di-n-octyltin dimaleate, di-n-octyltin dilaurate, di-n-butyltin dilaurate, etc. Particularly preferred tin compounds are di-n-octyltin dilaurate and di-n-butyltin dilaurate.

The vanadium compound used as the polymerization accelerator is preferably a tetravalent and/or pentavalent vanadium compound. Specific examples of the tetravalent and/or pentavalent vanadium compound include divanadium(IV) tetroxide, vanadium oxide acetylacetonate(IV), vanadyl oxalate(IV), vanadyl sulfate(IV), oxo-bis(1-phenyl-1,3-butanedionato)vanadium(IV), bis(maltolato)oxo-vanadium(IV), vanadium pentoxide(V), sodium metavanadate(V), and ammonium metavanadate(V).

Specific examples of halogen compounds used as polymerization accelerators include dilauryl dimethyl ammonium chloride, lauryl dimethyl benzyl ammonium chloride, benzyl trimethyl ammonium chloride, tetramethyl ammonium chloride, benzyl dimethyl cetyl ammonium chloride, and dilauryl dimethyl ammonium bromide.

Specific examples of aldehydes used as polymerization accelerators include terephthalaldehyde and benzaldehyde derivatives. Examples of benzaldehyde derivatives include dimethylaminobenzaldehyde, p-methyloxybenzaldehyde, p-ethyloxybenzaldehyde, and pn-octyloxybenzaldehyde. Among these, pn-octyloxybenzaldehyde is preferably used from the viewpoint of curability.

Specific examples of the thiol compound used as the polymerization accelerator include 3-mercaptopropyltrimethoxysilane, 2-mercaptobenzoxazole, decanethiol, and thiobenzoic acid.

A method for producing a radical polymerization crosslinkable water-soluble polymer according to the present invention, which has a polycarboxylic acid as a basic skeleton and radical polymerizable groups on the side chains in blocks, where the block copolymer connection sites migrate in a gradient manner, and a preparation method and physical properties of a medical and dental hardenable composition containing the radical polymerization crosslinkable water-soluble polymer produced by the method, which has a polycarboxylic acid as a basic skeleton and radical polymerizable groups on the side chains in blocks, where the block copolymer connection sites migrate in a gradient manner, will be described in detail below; however, the present invention is in no way limited to these descriptions.

Polymer synthesis examples 1 to 4
In a baked 100mL Schlenk polymerization tube with a three-way stopcock, 0.107g of benzoic peroxyanhydride was precisely weighed, 30mL of dehydrated and degassed anisole, and 0.1mL of nonane (internal standard for tracking polymerization reaction) were injected in this order with a syringe under argon flow. The Schlenk polymerization tube was magnetically stirred and 6.40g (50mmol) of tert-butyl acrylate, a radical polymerizable monomer, was added with a syringe, thoroughly stirred and homogenized, and then heated to 70°C in an oil bath to initiate polymerization. Samples were taken out at regular intervals under argon flow, and the monomer conversion was measured by gas chromatography. When the monomer conversion reached 50%, 1/3 of 4.30g (50mmol) of methyl acrylate was added, and samples were taken out again at regular intervals under argon flow, and the monomer conversion was measured by gas chromatography. When the monomer conversion rate reached 75%, 1/3 of methyl acrylate: 4.30g (50mmol) was added again, and samples were again taken out at regular intervals under argon flow, and the monomer conversion rate was measured by gas chromatography. Furthermore, when the monomer conversion rate reached 95%, 1/3 of methyl acrylate: 4.30g (50mmol) was added, and samples were taken out at regular intervals under argon flow, and the monomer conversion rate was measured by gas chromatography. When the monomer conversion rate reached 95%, heating was stopped, a small amount of oxygen was bubbled to stop the polymerization reaction, and the remaining monomer was distilled off by adding anisole in an evaporator. After that, vacuum drying was performed to obtain a very pale yellow powder. The obtained powder was added in its entirety to a 300mL Erlenmeyer flask equipped with an electromagnetic stirrer, dissolved in 100mL of acetone, and 10mL of 1N sodium hydroxide was added little by little with a Pasteur pipette, and only the methyl acrylate site was selectively hydrolyzed. The obtained hydrolyzed polymer was placed in a Visking tube and sodium hydroxide was removed by dialysis. After that, it was dried in a freeze dryer for 24 hours to obtain a powder of the polymer precursor. The entire amount of the precursor (gradient copolymer of polyacid and tert-butyl acrylate) was transferred to a 100mL three-necked flask reaction vessel equipped with a thermometer and a stirring blade, 30mL of acetone was added to dissolve it sufficiently, and a predetermined amount (50mmol) of radical polymerizable monomer having an isocyanate group at the end as described in Table 1-1 was dripped little by little with a microsyringe pump so that the liquid temperature did not exceed 80°C. After the dripping was completed, a maturation reaction was performed for 12 hours at 70°C. Then, 10mL of 1N trifluoroacetic acid was added little by little with a Pasteur pipette to hydrolyze the tert-butyl acrylate. After the dripping of 1N trifluoroacetic acid was completed, a maturation reaction was performed for 12 hours at 70°C to obtain a radical polymerization crosslinkable water-soluble gradient copolymer in which the target polycarboxylic acid was the basic skeleton and the ethylenically unsaturated group was gradiently bonded to the side chain.

Polymer synthesis examples 5 to 10
In a baked 100mL Schlenk polymerization tube with a three-way stopcock, 0.135g of benzoic peroxyanhydride was precisely weighed, 30mL of dehydrated and degassed anisole, and 0.1mL of nonane (internal standard for tracking polymerization reaction) were injected with a syringe under argon flow. The Schlenk polymerization tube was thoroughly stirred under magnetic stirring to completely dissolve. Then, 6.40g (50mmol) of tert-butyl acrylate, a radical polymerizable monomer, was added, thoroughly stirred to homogenize, and then heated to 70°C in an oil bath to initiate polymerization. Samples were taken out at regular intervals under argon flow, and the monomer conversion was measured by gas chromatography. When the monomer conversion rate reached 50%, 1/3 of 2-isocyanatoethyl acrylate: 7.06g (50mmol) was added, and samples were taken out under argon flow at regular intervals, and the monomer conversion rate was measured by gas chromatography. When the monomer conversion rate reached 75%, 1/3 of 2-isocyanatoethyl acrylate: 7.06g (50mmol) was added again, and samples were taken out under argon flow at regular intervals, and the monomer conversion rate was measured by gas chromatography. Furthermore, when the monomer conversion rate reached 95%, 1/3 of 2-isocyanatoethyl acrylate: 7.06g (50mmol) was added, and samples were taken out under argon flow at regular intervals, and the monomer conversion rate was measured by gas chromatography. When the monomer conversion rate reached 95%, the heating was stopped, a small amount of oxygen was bubbled to stop the polymerization reaction, and the remaining monomer was distilled off by adding anisole in an evaporator. 50 mmol of the radical polymerizable monomer having a carboxyl group or a hydroxyl group at the end, as described in Table 1-2, was gradually added to the solution using a microsyringe pump while heating in an oil bath so that the liquid temperature did not exceed 80°C. After the dropwise addition, a 12-hour maturation reaction was carried out at 70°C. The polymer was then added to n-hexane to precipitate. The polymer was purified by repeatedly dissolving in acetone and adding and precipitating in n-hexane. It was then dried in a vacuum to obtain a very pale yellow powder. The entire amount of the obtained powder was added to a 300 mL Erlenmeyer flask equipped with an electromagnetic stirrer, dissolved in 100 mL of acetone, and 10 mL of 1N trifluoroacetic acid was added little by little using a Pasteur pipette to hydrolyze the tert-butyl acrylate. The obtained hydrolyzed polymer was placed in a Visking tube and trifluoroacetic acid was removed by dialysis. The polymer was then dried in a freeze dryer for 24 hours to obtain the desired radical polymerization cross-linkable water-soluble polymer with a polycarboxylic acid as the base skeleton and radical polymerizable groups in block form on the side chains, in which the block copolymer connection sites shift in a gradient manner.

Polymer Comparative Synthesis Examples 1-4
In a baked 100mL Schlenk polymerization tube with a three-way stopcock, 242mg (1.0mmol: Comparative Synthesis Example 1), 484mg (2.0mmol: Comparative Synthesis Example 2), 726mg (3.0mmol: Comparative Synthesis Example 3), 968mg (4.0mmol: Comparative Synthesis Example 4) of benzoic peroxyanhydride (polymerization initiator), 0.1mL of nonane (internal standard for tracking polymerization reaction) were dissolved in 30mL of dehydrated anisole at room temperature. The Schlenk polymerization tube was stirred magnetically to completely dissolve the polymerization initiator. Then, 12.8g (100mmol) of tert-butyl acrylate, a radical polymerizable monomer, was added, thoroughly stirred and homogenized, and the mixture was heated to 70°C to initiate polymerization. Samples were taken at regular intervals, and the monomer conversion was measured by gas chromatography. When the monomer conversion rate reached 90%, the heating was stopped and the polymerization reaction was terminated, and the polymer precursor was then added to n-hexane to precipitate. The polymer precursor was purified by repeatedly dissolving it in acetone and adding it to n-hexane and precipitating it. It was then vacuum dried to obtain a very pale yellow powder. The entire amount of the obtained powder was added to a 300 mL Erlenmeyer flask equipped with an electromagnetic stirrer, dissolved in 100 mL of acetone, and 10 mL of 1N trifluoroacetic acid was added little by little with a Pasteur pipette to hydrolyze the tert-butyl acrylate. The obtained hydrolyzed polymer was placed in a Visking tube and excess trifluoroacetic acid, etc. were removed by dialysis. It was then dried in a freeze dryer for 24 hours to obtain a polycarboxylic acid powder.

Preparation of fluoroaluminosilicate powder (GI powder)
A mixture of 240g of SiO2, 204g _{of Al2O3} , _186g of CaO, and 52g of _CaF2 was melted in an alumina crucible using an electric Erema furnace, and then quenched with water to obtain a colorless and transparent glass lump. This glass lump was crushed in a vibration mill using alumina media and passed through a sieve with 42μm openings to obtain fluoroaluminosilicate glass powder (GI powder).

Examples 1 to 10
A liquid hardenable composition for medical and dental use was prepared according to the formulation shown in Table 2-1.

Comparative Examples 1 to 4
Comparative medical and dental hardenable composition liquids were prepared according to the compositions shown in Table 3-1.

Preparation of medical and dental hardenable composition powder <br/> A medical and dental hardenable composition powder was prepared with the composition shown in Table 3-2.

Physical Property Testing
The cement properties were evaluated according to ISO9917: Water-based cement standard (powder: 2.00g, liquid: 1.00g). Tables 4-1 and 5-1 show the physical property test results. The limit powder-liquid amount (g) means the amount of powder-liquid (amount of powder (g) per 1.0g of liquid) at which the coating degree measured 2 minutes after the start of mixing the powder-liquid (mixing time 60 seconds) exceeds 25 μm, and the greater the amount, the lower the initial viscosity of the mixture. In other words, it means that the viscosity of the mixture is low, the operation of the dental hygienist or other practitioner is easy, and the operability is excellent. From these test results, the medical and dental hardenable composition of the present invention, which contains a radical polymerization crosslinkable water-soluble polymer having a polycarboxylic acid as a basic skeleton and radical polymerizable groups in the side chains in blocks, and in which the block copolymer connection site shifts in a gradient, has a high compressive strength compared to the comparative examples, and also showed a very high limit powder-liquid amount. In addition, since the initial viscosity of the powder-liquid mixture is low, there is sufficient fluidity, and the water-soluble monomer that is eluted due to this is suppressed. In other words, it is believed that sufficient fluidity promotes reliable polymerization of the water-soluble monomer.

In the medical and dental fields, zinc phosphate cement, carboxylate cement, glass ionomer cement, and resin cement have been used as filling materials for bone defects and for bonding dental prostheses. Among them, resin-based restorative materials such as resin cement generally have higher toughness than zinc phosphate cement and carboxylate cement, and have been widely used in the fields of orthopedics and dentistry. However, these resin-based bioadhesive filling materials such as resin cement contain low-molecular radical polymerizable group-containing monomers such as 2-HEMA, and even after hardening, the remaining unreacted low-molecular monomers are eluted, which has a significant effect on biological tissues. However, the medical and dental curable composition produced by the present invention, which contains a radical polymerization crosslinkable water-soluble polymer having a polycarboxylic acid as a basic skeleton and radical polymerizable groups in the side chains in blocks, and in which the block copolymer connection sites move in a gradient manner, has higher toughness than the medical and dental curable compositions of the prior art, has the effect of obtaining a curable composition that does not elute low-molecular monomers and is easy to handle, and can be said to have great potential for industrial use.

Claims (9)

A method for producing a radical polymerization crosslinkable water-soluble polymer having a polycarboxylic acid represented by the structural formula [Chemical Formula 1] as a basic skeleton and having radical polymerizable groups in block form on the side chains, in which the block copolymer connection sites migrate in a gradient manner, characterized in that the starting material for the chemical structural site exhibiting ion reactivity is an acrylic acid ester and/or a methacrylic acid ester.

In the formula, A has a chemical structure that exhibits ion reactivity, B has a chemical structure that exhibits radical polymerizability, and Grad in the formula indicates the portion that transitions from A to B in a gradient manner. Additionally, a and b indicate structures derived from a polymerization initiator or a terminator portion. In the formula, m and n indicate the number of repetitions, both of which are within the range of 1 to 1000, and A and B are covalently bonded in a gradient block shape, with a molar mass distribution Mw/Mn exceeding 1.8.
A method for producing a radical polymerization crosslinkable water-soluble polymer having a polycarboxylic acid represented by the structural formula [Chemical Formula 2] as a basic skeleton and having radical polymerizable groups in block form on the side chains, in which the block copolymer connection sites migrate in a gradient manner, characterized in that the starting material for the chemical structural site exhibiting ion reactivity is an acrylic acid ester and/or a methacrylic acid ester.

In the formula, A has a chemical structure exhibiting ion reactivity, B has a chemical structure exhibiting radical polymerizability, and Grad in the formula indicates the site where B transitions to A in a gradient manner. Additionally, a and b indicate structures derived from a polymerization initiator or a terminator portion. In the formula, m and n indicate the number of repetitions, both of which are within the range of 1 to 1000, and A and B are covalently bonded in a gradient block shape, with a molar mass distribution Mw/Mn exceeding 1.8.
A method for producing a radical polymerization crosslinkable water-soluble polymer, characterized in that the polymerization method described in claims 1 and 2 is free radical polymerization, which has a polycarboxylic acid as a basic skeleton and radical polymerizable groups in block form on the side chains, and in which the block copolymer connection sites migrate in a gradient manner.
1) Step 1 of polymerizing an acrylic ester A and/or a methacrylic ester A by the method according to claim 3;
2) Step 2: Adding acrylic acid ester B and/or methacrylic acid ester B to the polymer synthesized in step 1 in equal portions at least three times to carry out block polymerization by the method according to claim 3;
3) step 3 of hydrolyzing the obtained polyacrylic acid ester A and/or polymethacrylic acid ester A;
4) reacting the carboxyl group produced by the hydrolysis in step 3 with a compound having an isocyanate group and a radical polymerizable group in the same molecule via decarboxylation to form an amide bond;
5) Step 5: Hydrolyzing polyacrylic acid ester B and/or polymethacrylic acid ester B to convert it into polycarboxylic acid
The method for producing a radical polymerization crosslinkable water-soluble polymer according to claim 1 or 2, which has a polycarboxylic acid as a basic skeleton and radical polymerizable groups in block form on the side chains, and in which the block copolymer connection sites move in a gradient manner, is achieved by going through the above five steps.
A method for producing a radical-polymerizable crosslinkable water-soluble polymer having a polycarboxylic acid as a basic skeleton and radically polymerizable groups in block form on the side chains according to claim 4, characterized in that acrylic acid ester A and methacrylic acid ester A are tert-butyl esters, and acrylic acid ester B and methacrylic acid ester B are methyl esters and/or ethyl esters, in which the block copolymer connection sites migrate in a gradient manner.
A method for producing a radical-polymerizable crosslinkable water-soluble polymer having a polycarboxylic acid as a basic skeleton and radically polymerizable groups in block form on the side chains according to claim 4, characterized in that acrylic acid ester A and methacrylic acid ester A are methyl esters and/or ethyl esters, and acrylic acid ester B and methacrylic acid ester B are tert-butyl esters, in which the block copolymer connection sites migrate in a gradient manner.
1) Step 1 of polymerizing an acrylic ester A and/or a methacrylic ester A by the method according to claim 3;
2) adding a radical polymerizable monomer having a hydroxyl group to the polymer synthesized in step 1 in equal portions at least three times, and polymerizing the polymer by the method according to claim 3;
3) reacting a compound having an isocyanate group and a radical polymerizable group in the same molecule with the hydroxyl group of the block copolymer produced in the step 2 to form a urethane bond;
4) a step of hydrolyzing the ester bonds of the polyacrylic acid ester A and/or the polymethacrylic acid ester A to generate carboxyl groups;
The method for producing a radical polymerization crosslinkable water-soluble polymer according to claim 1 or 2, which has a polycarboxylic acid as a basic skeleton and radical polymerizable groups in block form on the side chains, and in which the block copolymer connection sites move in a gradient manner, is achieved by the above four steps.
8. A method for producing a radically polymerizable crosslinkable water-soluble polymer having a polycarboxylic acid as a basic skeleton and radically polymerizable groups in side chains in blocks, in which the block copolymer connection sites move in a gradient manner, as described in claim 7, wherein the radically polymerizable monomer having a hydroxyl group is at least one selected from the group consisting of 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, ethylene glycol monoacrylate, ethylene glycol monomethacrylate, diethylene glycol monoacrylate, diethylene glycol monomethacrylate, triethylene glycol monoacrylate, and triethylene glycol monomethacrylate.
A method for producing a radical polymerization crosslinkable water-soluble polymer having a polycarboxylic acid as a basic skeleton and radical polymerizable groups in block form on the side chains according to claim 7, characterized in that the acrylic acid ester A and the methacrylic acid ester A are at least one selected from the group consisting of tertiary butyl ester, methyl ester and ethyl ester, and in which the block copolymer connection sites migrate in a gradient manner.